Osteoarthritis (OA) is the most common rheumatic disease of the elderly. As part of the ongoing studies of OA in the Baltimore Longitudinal Study of Aging (BLSA) we have evaluated the association of metabolic and physiologic factors with the presence distribution, and progression of hand and knee OA in both sexes. In 234 men and 95 women in the BLSA, aged 60 and above, definite knee OA was present in 65% of those with pain compared to 34% of those without knee pain. Prevalence of self- reported pain is significantly associated with the severity of the grade of OA in the knee.In 130 subjects with longitudinal knee xrays, we found that incidence or progression of OA occurred in 22 (17%) with grade 0-2 osteophyte changes at baseline, over a mean follow-up of 3.8q1.1 yrs; and that both age and BMI at baseline significantly predicted time to incidence or progression. In 465 men and 275 women aged 40 and above, we found that current smoking is associated with a decreased risk of osteophyte formation and knee OA in women independent of age and BMI. We found that subjects aged 40 and above with current knee pain have significantly lower aerobic capacity (AC) than those without knee pain adjusted for radiographic changes of knee OA, confirming the hypothesis that AC is diminished in persons with symptomatic knee OA. In 340 men and 208 women aged 40 and above, mean spine bone mineral density (BMD) was significantly greater in those with knee OA, after adjustment for age and BMI. There was no association between hip BMD and knee OA features. In our evaluation of familial aggregation of hand and generalized OA in the BLSA, we found clinically relevant sibling correlations for OA of the distal interphalangeal joints, after adjustment for age and gender, but no association for other hand sItes, for knee OA, or for polyarticular OA (hand and knee).